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Int J Clin Exp Pathol 2011;4(8):775-781

Original Article
C-kit expression in human osteosarcoma and in vitro assays

Luciana NO Miiji, Antonio S Petrilli, Sebastian Di Cesare, Alexandre N Odashiro, Miguel N Burnier Jr, Silvia R de Toledo, Reynaldo Jesus
Garcia, Maria Teresa S Alves

Federal University of São Paulo, Department of Pathology, São Paulo, Brazil; Pediatric Oncology Institute (IOP, GRAACC/UNIFESP)/Federal
University of São Paulo, Department of Pediatrics, São Paulo, Brazil; The Henry C Witelson Ocular Pathology Laboratory, McGill University,
Montreal, Quebec, Canada; Department of Pathology, Centre Hospitalier afillie Universitaire de Quebec, Quebec, Canada; Federal University of
São Paulo, Department of Orthopedic Surgery, São Paulo, Brazil

Received September 20, 2011; accepted October 23, 2011; Epub November 3, 2011; Published November 30, 2011

Abstract: Biologic agents targeting oncogenes have encourage researchs trying to correlate the role of tyrosine kinase in the pathogenesis of
tumours. Osteosarcoma is a high grade aggressive neoplasm with poor survival. Our aim was to investigate c-kit immunoexpression, its
prognostic relevance for patients with osteosarcoma, and the effect of imatinib mesylate (STI571) on proliferation and invasion of the human
osteosarcoma cell line.A retrospective immunohistochemical study was performed on archival formalin-fixed paraffin-embedded specimens
from 52 patients with high-grade primary osteosarcoma of extremities treated at the Pediatric Oncology Institute (IOP, GRAAC) and archived in
the Department of Pathology, Federal University of São Paulo. Only pre-chemotherapy specimens were analyzed. Strongly stained cytoplasm
and membrane cells were taken as positive. Human osteosarcoma cells from line MG-63 were incubated and the inhibitory effect of imatinib
mesylate (STI571) on cell proliferation and invasion was studied. In 24 cases (46.15%), c-kit was expressed by the cells and c-kit-positive
tumors exhibited lower necrosis post-chemotherapy. No correlation was found between c-kit expression and overall and disease-free survival.
Imatinib mesylate decreased the rates of cell growth of osteosarcoma cells in low doses and invasion in high doses C-kit-positive tumors had
worse response to chemotherapy and imatinib mesylate can play a role in blocking or decreasing the rate of growth of osteosarcoma cells, but
not the invasive capacity of these neoplastic cells. These data suggested that imatinib mesylate could be a therapeutic target of strategies
against osteosarcoma tumors. Further studies are necessary to confirm this indication.

Keywords: Osteosarcoma, c-kit, immunohistochemistry, in vitro assays, prognosis

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Address all correspondence to:
Dr. Luciana NO Miiji
Rua Marechal Candido Mariano Rondon
2372 (Vila Cidade), 79002-201 - Campo Grande - MS, Brazil.
Tel: 55-67-3029-7346; Fax: 55-67-3027-7008
E-mail: lucianaom@yahoo.com.br